Monitoring phenylalanine concentrations in the follow-up of phenylketonuria patients: An inventory of pre-analytical and analytical variation

Karlien L.M. Coene*, Corrie Timmer, Susan M.I. Goorden, Amber E. ten Hoedt, Leo A.J. Kluijtmans, Mirian C.H. Janssen, Alexander J.M. Rennings, Hubertus C.M.T. Prinsen, Mirjam M.C. Wamelink, George J.G. Ruijter, Irene M.L.W. Körver-Keularts, M. Rebecca Heiner-Fokkema, Francjan J. van Spronsen, Carla E. Hollak, Frédéric M. Vaz, Annet M. Bosch, Marleen C.D.G. Huigen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Reliable measurement of phenylalanine (Phe) is a prerequisite for adequate follow-up of phenylketonuria (PKU) patients. However, previous studies have raised concerns on the intercomparability of plasma and dried blood spot (DBS) Phe results. In this study, we made an inventory of differences in (pre-)analytical methodology used for Phe determination across Dutch laboratories, and compared DBS and plasma results. Methods: Through an online questionnaire, we assessed (pre-)analytical Phe measurement procedures of seven Dutch metabolic laboratories. To investigate the difference between plasma and DBS Phe, participating laboratories received simultaneously collected plasma-DBS sets from 23 PKU patients. In parallel, 40 sample sets of DBS spotted from either venous blood or capillary fingerprick were analyzed. Results: Our data show that there is no consistency on standard operating procedures for Phe measurement. The association of DBS to plasma Phe concentration exhibits substantial inter-laboratory variation, ranging from a mean difference of −15.5% to +30.6% between plasma and DBS Phe concentrations. In addition, we found a mean difference of +5.8% in Phe concentration between capillary DBS and DBS prepared from venous blood. Conclusions: The results of our study point to substantial (pre-)analytical variation in Phe measurements, implicating that bloodspot Phe results should be interpreted with caution, especially when no correction factor is applied. To minimize variation, we advocate pre-analytical standardization and analytical harmonization of Phe measurements, including consensus on application of a correction factor to adjust DBS Phe to plasma concentrations.

Original languageEnglish
Pages (from-to)70-79
Number of pages10
JournalJIMD Reports
Issue number1
Early online date22 Nov 2020
Publication statusPublished - 1 Mar 2021

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© 2020 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.


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